SYNTHESIS AND ANALGESIC ACTIVITY OF 1-SUBSTITUTED DERIVATIVES OF 4-METHOXYCARBONYL-4-N-PROPIONYLANILINEPIPERIDINE

In this paper, the synthesis and analgesic activities of a series of 1-substituted derivativesof N'1-(2-phenylethyl)-4-methoxycarbonyl-4-piperidinyl-N-propionylaniline (4-methoxycarbonyl fentanyl) are reported. Preliminary pharmacological results showed that most compounds in this series exhibited typical morphine-like action and that replacement of β-phenyl group in the 1-position of piperidine ring of 4-methoxycarbonyl fentanyl by some substituents e.g., some substituted vinyl groups, heterocyclic (or alcyclic) radicals, alkyl groups or N-methylaniline group, can keep strong analgesic activity. Especially, some substituted vinyl groups were found to be effective groups which could replace 1-β-pheny group of 4-methoxycarbonyl fentanyl. Compounds N-1-(3,4-dimethyl-3-pentenyl)-4-methoxycarbonyl-4-piperidinyl-N-propionylaniline(1321)and N-1-(4-methyl-3-pentenyl)-4-mothoxyearbonyl-4-piperidinyl-N-propionylaniline(1302) exhibited higher analgesic activity than that of 4-methoxycarbonyl fentanyl.